Abstract 389P
Background
Better biomarkers are urgently needed to optimize the management of pancreatic ductal adenocarcinoma (PDAC) patients receiving neoadjuvant therapy (NT) to improve current disappointing recurrence (70-90%) and long-term survival (10-43%) rates. This retrospective study investigated whether Serum mucin 5 AC (Se-MUC5AC) might be a useful biomarker in the NT setting.
Methods
Serum samples collected from January 2010 to June 2021 were obtained from the Ohio State University biorepository. We performed enzyme-linked immunoassays using a human MUC5AC kit (NBP2-76703). Univariate (UV) and multivariate (MV) Cox regression models were used to quantify progression-free survival (PFS); clinical and pathological variables were adjusted in the MV models. UV logistic regression analysis was utilized to examine the association of Se-MUC5AC with pathological features and survival.
Results
Overall, 23 samples (19 FOLFIRINOX, 3 gemcitabine/nab-paclitaxel, 1 FOLFOX) were available for analysis. The median age was 66 years, and 52% were males. Se-MUC5AC was associated with a) treatment response, margin status, and residual disease (R0 vs. R1/R2) (all p<0.05); b) PFS on both UV (Hazard Ratio (HR) of 1.4, 95% Confidence Interval (CI) of 1.07 to 1.82, p=0.01) and MV (HR of 49.2, 95% CI, 4.4 to 1008.3, p=0.002) analyses; and c) PFS in pre-surgery models along with carbohydrate antigen 19-9 (CA19.9) measured on the same day alone (HR of 1.47, 95% CI, 1.06 to 1.93, p=0.04), with CA 19-9 and NT regimen (HR of 1.44, 95% CI, 1.12 to 1.93, p=0.01), with CA19-9, NT regimen, and CA 19-9 at diagnosis (HR of 1.52, 95% CI, 1.1 to 2.09, p=0.007). With mean levels as cut-off (1.82 ng/mL), compared to patients with high se-MUC5AC (n=7), those with low MUC5AC (n=16) had larger (> 2 cm) tumors and were more likely to have had an R0 resection, as well as better PFS (8 vs. 4 months, p=0.04). These data suggest that Se-MUC5AC levels may reflect tumor cell turnover and aggressive clinical behavior and that CA 19-9 measures tumor burden.
Conclusions
Se-MUC5AC, alone or combined with CA 19-9, can predict pathological and survival outcomes among patients treated with NT for PDAC before resection. Future, larger studies are needed to confirm this finding.
Legal entity responsible for the study
The authors.
Funding
The Ohio State University Comprehensive Cancer Center.
Disclosure
A. Manne: Financial Interests, Personal, Advisory Role: Pfizer, AstraZeneca. R.K. Paluri: Financial Interests, Personal, Advisory Role: Ipsen, Exelixis, Seagen. A. Kasi: Financial Interests, Personal, Advisory Role: Ipsen, Cardinal Health; Financial Interests, Institutional, Funding: Tesaro, Astellas Pharma, Rafael Pharmaceuticals, Geistlich, Cardiff, FibroGen, Bavarian Nordic, Novocure, Cend Therapeutics, Ability Pharma. D. Sohal: Financial Interests, Personal and Institutional, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Incyte, Seagen; Financial Interests, Personal, Advisory Role: Replimune, Cancer Common, TranThera, Totus Medicines, Valar Labs; Financial Interests, Personal, Research Grant: Aadi, Elevar; Financial Interests, Institutional, Research Grant: Aadi, Ability Pharma, Amgen, Apexigen, Astellas, Bexion, BMS, FibroGen, Genentech, Hengrui, Merck, Mirati, NextCure, PanCan, Regneron, Roche, Trimvira. M. Khushman: Financial Interests, Personal, Stocks/Shares: Cardiff Oncology; Financial Interests, Personal, Advisory Role: Muerus, Cardinal Health, TriSalus Life Sciences; Financial Interests, Personal, Speaker’s Bureau: Caris Life Sciences; Financial Interests, Institutional, Research Grant: AbbVie, FOG Pharma, IgM Biosciences, Torl Biotherapeutics. All other authors have declared no conflicts of interest.